KR20120029130A - Biomedical implants comprising surface-modified metal particles and biodegradable polymers, its use for suppressing inflammation, and preparation method thereof - Google Patents

Abstract

PURPOSE: Biomedical implants containing surface-modified metal particles and biodegradable polymers, the use of the same for suppressing inflammation, and a method for preparing the same are provided to improve the mechanical characteristic of the biodegradable polymers and to suppress the inflammation and cytotoxicity. CONSTITUTION: Biomedical implants contain surface-modified metal particles and biodegradable polymers. Acidic materials generated from the degradation of the biodegradable polymers are neutralized with basic metal particles to suppress inflammation. The basic metal particles are selected from a group including particles of a selected metal and particles of a selected metal compound. The metal is selected from a group including alkali metals and alkali earth metals. The metal compound is selected from a group including the hydroxide of alkali metals, the oxide of alkali metals, the hydroxide of alkali earth metal, and the oxide of alkali earth metal.

Description

Bio-implants comprising surface modified metal particles and biodegradable polymers, uses for inhibiting inflammation thereof, and methods for preparing the same.

FIELD OF THE INVENTION The present invention relates to biografts comprising surface modified metal particles and biodegradable polymers, their use as inhibitors of inflammation and methods of making the same.

Recent advances in medical technology have used artificial organs or implantable materials to replace and repair damaged organs in the human body. Such materials are called living implants. BACKGROUND OF THE INVENTION In vivo implants, the scope of application thereof is gradually widening. Accordingly, much research is being conducted on the development of living implants. Materials used in such living implants include polymers, metals, ceramics, composite materials, and the like. However, materials used in the human body must be biocompatibility, blood compatibility in contact with blood, and tissue compatibility in contact with biological tissues or cells other than blood. compatibility is required, the biomaterials available are very limited.

Therefore, polymer materials that are harmless to the human body but have excellent moldability and stable physical properties are in the spotlight, and in particular, biodegradable polymers decompose after a certain period of time, and thus, self-defense functions appear after transplantation of a living body implant. The foreign body reaction by can be minimized.

However, biodegradable polymers have relatively poor physical properties compared to other polymers, and are biodegradable, so that lactic acid, glycolic acid, capric acid hydroxide, maleic acid, phosphazene, butyl hydroxide, ethoxyacetic acid, sebacic acid, alcohol, trimethylene Acidic substances such as lycol, amino acids, formalin, alkylcyanoacrylates are produced, causing inflammatory reactions and cytotoxicity problems in the human body.

Despite the above drawbacks, biodegradable polymers are widely used in living implants because of their ability to completely decompose after a certain period of time, and several methods have been proposed to mitigate the inflammatory response of biodegradable polymers.

As an example, biodegradable polymers used as implants contain ester-based non-steroidal anti-inflammatory drugs such as salicylic acid and acetylsalicylic acid to obtain anti-inflammatory effects and improve physical properties. A study was undertaken ( J. Mater. Sci. Mater. Med ., 13, 1051-1055, 2002) and pyridoxal-5-phosphate was coated on the stent to inhibit inflammation and restenosis. A method has been proposed (WO 2006/056038). In addition, a method of inhibiting cellular inflammation by expressing COX-2 protein and iNOS protein using Tahibo extract has been proposed (Korean Patent Publication No. 2008-0092263), and occurs during an inflammatory reaction using nanoparticles of gold and silver. A method of inducing nitric oxide production inhibition is also being studied (Korean Patent Publication No. 2009-0080855).

However, the methods exemplified above are methods for suppressing inflammation caused by the inclusion of anti-inflammatory agents in the biomaterial, and there is a fear of side effects due to drug use.

In addition, a method of fundamentally inhibiting the generation of acidic substances by decomposition of biodegradable polymers has not been proposed. That is, the cellular inflammatory response due to the low pH of the acidic substance is always caused by biodegradation when the biodegradable polymer is used, but there is no fundamental solution yet, and the mechanical properties of the biodegradable polymer are improved. There is a limit.

The present invention is to overcome the limitations of the prior art as described above, the object of which is that the low pH acidic material produced by decomposing the biodegradable polymer of the living implant is neutralized by harmless and degradable basic metal in the human body, It is to provide a method for inhibiting the inflammatory response and cytotoxicity caused by acidic substances.

Another object of the present invention is to improve the mechanical properties of biodegradable polymer materials by modifying the surface of the basic metal particles to control the basic properties and at the same time increasing the compatibility between the basic metal particles and the biodegradable polymer. To provide.

The object of the present invention as described above is achieved by the following.

(1) A living implant comprising a basic metal particle surface modified with a polymer and a biodegradable polymer.

(2) modifying the surface of the basic metal particles with a polymer to obtain surface modified metal particles, and (b) mixing the surface modified metal particles obtained in step (a) with a biodegradable polymer to obtain a biodegradable biograft. Comprising the step of preparing a method of producing a biomaterial of (1).

(3) (a) modifying the surface of the basic metal particles with a polymer to obtain surface modified metal particles, and (b ') mixing the surface modified metal particles obtained in step (a) with a biodegradable polymer to provide a surface of the living implant. A method for producing a living body implant of (1), comprising the step of coating on.

According to the present invention, a living implant comprising surface modified metal particles and a biodegradable polymer, a use thereof for inhibiting inflammation, and a method of manufacturing the same are provided.

In the present invention, by mixing the biodegradable polymer with the surface-modified basic metal particles, the mechanical properties of the biodegradable polymer material can be improved, and the basic metal can neutralize the acidic material generated while the biodegradable polymer is decomposed. It is possible to significantly improve the inflammatory response and cytotoxicity caused by acidic substances.

Therefore, according to the present invention, a bio-implant can be prepared directly with a basic metal particle and a biodegradable polymer surface-modified with a polymer, or a basic metal particle and a biodegradable polymer with a surface-modified polymer can be used as a polymer, metal, ceramic, and composite material. Conventional biological implants of, for example, stents, surgical sutures, tissue regeneration supports, bio-nanofibers, cardiovascular materials such as hydrogels or biosponges, dental materials such as pins, screws, rods, and nerves / orthodontics / It may be usefully used as a method for coating a plastic surgery material or the like.

The present invention relates to a biological implant comprising surface modified basic metal particles and a biodegradable polymer, the use thereof for inhibiting inflammation and a method of producing the same.

The basic metal particles are particles of a metal compound selected from the group consisting of particles of a metal selected from the group consisting of alkali metals and alkaline earth metals, hydroxides of alkali metals, oxides of alkali metals, hydroxides of alkaline earth metals and oxides of alkaline earth metals. It may be one or more selected from the group consisting of. The alkali metal or alkaline earth metal may be lithium, beryllium, sodium, magnesium, potassium, calcium, rubidium, strontium, barium, cesium, francium or radium, and the metal compound may be lithium hydroxide, beryllium hydroxide, sodium hydroxide, magnesium hydroxide. , Potassium hydroxide, calcium hydroxide, rubidium hydroxide, strontium hydroxide, barium hydroxide, cesium hydroxide, francium hydroxide, radium hydroxide, magnesium oxide, sodium oxide, lithium oxide, sodium oxide, manganese oxide, potassium oxide, calcium oxide, barium oxide, oxide It may be one or more selected from the group consisting of cesium and radium oxide.

The surface area of the metal particles may be changed according to diameters, so that the characteristics of the degree of neutralization and the rate of neutralization of the metal particles may vary. In addition, in order to modify the surface of the metal particles, the particle size should be at least 1 nm, and if the size of the metal particles exceeds 1 mm, cracks are generated in the polymer matrix, which is undesirable. Thus, the preferred diameter range of the metal particles is 1 nm to 1 mm.

The polymer used for surface modification of the metal particles is lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate, alkanoate hydroxide, peptide, cyanoacrylate, lactic acid, glycolic acid, caproic acid hydroxide, It may be a polymer produced by the polymerization of at least one monomer selected from the group consisting of maleic acid, phosphazene, amino acid, butyric acid hydroxide, sebacic acid, ethoxyacetic acid hydroxide and trimethylene glycol.

In addition, the polymer used for the surface modification of the basic metal particles is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide -co-caprolactone, polydioxanone, polytrimethylenecarbonate, polyglycolide -co-dioxoneone, polyamide ester, polypeptide, polyorthoester type, polymaleic acid, polyphosphazene, polyanhydride, It may be one or more selected from the group consisting of polyceba anhydride, polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate.

It is preferable that the content of the polymer is 5 to 95% by weight and the content of the basic metal particles is 5 to 95% by weight based on the total weight of the surface-modified basic metal particles. In the surface-modified basic metal particles, since the ratio of the surface modification layer of the metal particles is changed according to the weight ratio between the basic metal particles and the polymer, the neutralization rate and the degree of neutralization of the metal particles may be controlled. If it is less than 5% by weight, the content of the polymer modified on the surface of the metal particles is too large to lose the neutralizing function of the basic metal particles, and if the content of the metal particles exceeds 95% by weight is not preferable because the surface modification of the metal particles is not sufficient. .

The biodegradable polymer is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone , Polytrimethylene carbonate, polyglycolide-co-dioxone, polyamide ester, polypeptide, polyol isoester type, polymaleic acid, polyphosphazene, polyanhydride, polycephaanhydride, polyhydroxide alkano It may be one or more selected from the group consisting of eight, polyhydroxybutyrate and polycyanoacrylate.

The living implant according to the present invention may be composed of a surface-modified basic metal particles and a biodegradable polymer, or may be a surface-modified basic metal particles and a biodegradable polymer coated on a conventional biological implant. have.

When the biological implant is composed of a basic metal particle and a biodegradable polymer surface-modified with a polymer, the content of the basic metal particle surface-modified with a polymer to the total weight of the biological implant is within the range of 1 to 99% by weight, The content of biodegradable polymer is controlled in the range of 1 to 99% by weight. In the present invention, by controlling the content between the metal particles and the biodegradable polymer within the above range it is possible to control the physical properties and the degree of neutralization of the living implant.

The bio-implant may be a cardiovascular material such as a stent, a surgical suture, a support for tissue regeneration, a bio-nanofiber, a hydrogel or a biosponge, a dental or nerve / orthopedic / plastic surgery biomaterial such as a pin, a screw or a rod It may be, but any living implant other than these may be used.

When the living body implant is a coating of a basic metal particle and a biodegradable polymer with a surface modified with a polymer in a conventional living body implant, the coating is based on the total weight of the coating of the basic metal particle surface modified with a polymer 1 to 99% by weight, may contain 1 to 99% by weight of the biodegradable polymer. The nature of the degree of neutralization can be changed by varying the content of basic metal particles in the coating layer. In the present invention, by adjusting the content ratio of the basic metal particles and the biodegradable polymer in the coating layer can be applied to a wide range of living implants.

The conventional bio-implant may be any bio-implant made of metal, ceramic, composite material, non-degradable polymer or biodegradable polymer material, specifically, the material is iron, copper, gold, silver, platinum, stainless steel, Metals selected from cobalt-chromium, platinum-chromium, cobalt alloys, titanium, titanium alloys, tantalum, nickel-titanium, nickel, nickel alloys, magnesium and magnesium alloys, apatite hydroxide, TeCP, DCP, NaH ₂ PO ₄ , α- Ceramic, polyethylene, polypropylene, polyvinyl alcohol, polyvinyl chloride, polystyrene, poly selected from the group consisting of TCP, Glycerophosphate, PHA, Brushite, β-TCP, MCPM, MgHPO ₄ , Na ₄ P ₂ O ₇ and CaSO ₄ Acrylic resins such as carbonate, polyether ether ketone (PEEK), polyamide, polyacetal, polythiophene, polyethylene oxide, polytetrafluoroethylene, PMMA, polyurethane, e Non-degradable polymers, polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide selected from the group consisting of resins and polysiloxanes -co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide -co-dioxoneone, polyamide ester, polypeptide, polyol isoester type, polymaleic acid, polyphosphazene, polyanhydride, poly It is selected from the group consisting of biodegradable polymers selected from the group consisting of seba anhydride, polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate.

In addition, the present invention relates to a method for producing a living implant comprising a basic metal particles and a biodegradable polymer surface-modified with a polymer, the method (a) to obtain a surface-modified metal particles by modifying the surface of the basic metal particles with a polymer And (b) mixing the surface modified metal particles with a biodegradable polymer to produce a biodegradable biograft.

In step (a), monomers are ring-opened or condensation polymerized on the surface of the basic metal particles, or the basic metal particle core is encapsulated in a core-shell form in the polymer shell to obtain surface modified metal particles.

When modifying the surface using ring-opening polymerization, 5 to 95% by weight of basic metal particles is used based on the total weight of the surface modified metal particles obtained in step (a). If the amount of the basic metal particles is less than 5% by weight, the polymer content on the surface of the metal particles is so large that the neutralization function of the metal particles is lost. If the amount of the metal particles is more than 95% by weight, the surface of the metal particles is not sufficiently modified. Not desirable

The ring opening reaction is tin powder, stannious octoate, dibutyl tin dilaurlate, dibutyl tin dibromide. A conventional ring-opening polymerization catalyst selected from the group consisting of dibutyl tin dichloride, stannous chloride, stannous chloride, tin oxide, zinc powder, diethyl zinc, zinc octoate, zinc chloride and dodecylbenzenesulfonic acid, The reaction is carried out under reduced pressure using 0.001 to 5.0% by weight based on the total weight of the surface modified metal particles obtained in step (a). In the ring-opening polymerization reaction, the optimum polymerization reaction temperature for opening the monomer is 50 to 300 ℃, the reaction time is 1 to 60 hours.

When modifying the surface using condensation polymerization, 5 to 95% by weight of basic metal particles are used based on the total weight of the surface modified metal particles obtained in step (a). If the amount of the basic metal particles is less than 5% by weight, the polymer content on the surface of the metal particles is so large that the neutralization function of the metal particles is lost. If the amount of the metal particles is more than 95% by weight, the surface of the metal particles is not sufficiently modified. Not desirable

The condensation reaction is carried out by heating under reduced pressure. The optimum polymerization reaction temperature for the condensation polymerization of the monomer during the condensation polymerization is 50 to 300 ℃, the reaction time is 1 to 60 hours.

In the case of surface modification by encapsulating in a core-shell form, the surface modification polymer is dissolved in a solvent, and the basic metal particles are dispersed at a speed of 10 to 100,000 rpm using an ultrasonic or homogenizer, and then the surface modification is recovered. Metal particles can be obtained. The solvent may be at least one selected from the group consisting of chloroform, acetone, tetrahydrofuran, dioxane, acetonitrile, methylene chloride, toluene, xylene, benzene, and hexafluoroisopropane.

The monomers and polymers used for surface modification of the metal particles in step (a) are as described above.

In step (b), the biodegradable biograft may be prepared by mixing 1 to 99 parts by weight of the surface modified metal particles obtained in step (a) with 1 to 99 parts by weight of the biodegradable polymer, and the matrix of the biodegradable polymer. Since the degree of neutralization and the rate of neutralization of the living implant increases as the content of the surface modified metal particles increases, the degree of neutralization and the rate of neutralization of the living implant can be controlled by controlling the content of the surface modified metal particles.

Another method for producing a biograft comprising a basic metal particle and a biodegradable polymer surface-modified with a polymer according to the present invention is to substitute the surface-modified metal particle obtained in step (a) instead of step (b). And mixing the biodegradable polymer with the surface of the living implant. Thus, this method yields a conventional biological implant coated with a mixture of basic metal particles and biodegradable polymers surface-modified with a polymer.

In step (b '), 1 to 99 parts by weight of the surface-modified metal particles obtained in step (a) and 1 to 99 parts by weight of the biodegradable polymer are mixed, and the mixture is mixed with conventional metals, ceramics, composites, and non-degradable materials. Coat the surface of the biograft of polymer or biodegradable polymer material. By varying the content of surface modified metal particles in the coating layer, the nature of the degree of neutralization of the living implant can be controlled.

The coating method may be any of known coating methods, including ultrasonic method, spray method, dipping method, spin coating method, electrolyte coating method, chemical / physical vapor deposition method.

The types of biodegradable polymers used in the steps (b) and (b '), the types of living implants, and the materials thereof are as described above.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are only preferred examples of the present invention, and the present invention is not limited to the scope of these examples.

In order to evaluate the characteristics of the living implants prepared in the following Examples and Comparative Examples, mechanical tensile strength was measured by Instron according to the method of ASTM D638, and the pH change after 8 weeks of biodegradation was confirmed. In addition, the cellular inflammatory response and cytotoxicity were evaluated by the degree of COX-2 expression and cytotoxicity test methods, respectively.

Example 1:

50 parts by weight of magnesium hydroxide and 50 parts by weight of lactide were added to the dried glass reactor, and 0.1 wt% of tin octosan was diluted with toluene based on the total weight of the reactants (magnesium hydroxide and lactide) as a catalyst. The glass reactor containing the reactants was maintained under vacuum at 70 ° C. for 6 hours with stirring to completely remove toluene and water. The sealed glass reactor temperature was adjusted to 140 ° C. and ring-opened polymerized for 30 hours with stirring in an oil bath. After completion of the polymerization, the polymer was recovered, and the recovered polymer was put in chloroform, stirred for 1 hour or more, and filtered to remove homopolymer and unreacted residue, thereby finally obtaining magnesium hydroxide particles whose surface was modified with polylactide.

Next, 30 parts by weight of surface-modified magnesium hydroxide particles prepared by the above method were mixed with 70 parts by weight of polylactide biodegradable polymer to prepare a fully biodegradable stent, and then measured for tensile strength, pH change, inflammatory response and cytotoxicity. It was. As shown in Table 1, the tensile strength was greatly improved, the pH became neutral, the inflammatory response was completely suppressed, and no cytotoxicity appeared.

Example 2:

60 parts by weight of calcium hydroxide and 40 parts by weight of lactic acid were added to the glass reactor, and the mixture was kept in a vacuum at 70 ° C. for 6 hours while stirring to completely remove moisture. The glass reactor temperature was adjusted to 140 ° C. and condensation polymerization in an oil bath for 30 hours. The recovered polymer was removed in the same manner as in Example 1 to obtain calcium hydroxide particles whose surface was modified with polylactide.

Next, a surgical suture was prepared by mixing 20 parts by weight of the surface-modified calcium hydroxide particles prepared by the above method and 80 parts by weight of polyglycolide, a biodegradable polymer, to measure tensile strength, pH change, inflammatory response and cytotoxicity. . As shown in Table 1, the results were similar to Example 1.

Example 3:

10 parts by weight of polycaprolactone is dissolved in 85 parts by weight of chloroform, and 5 parts by weight of magnesium oxide is added thereto, followed by ultrasonication for 60 minutes to disperse completely, and the core-shell method of oxidation of a surface modified with polycaprolactone. Magnesium particles were prepared.

15 parts by weight of the surface-modified magnesium oxide particles prepared by the above method and 85 parts by weight of polylactide-co-glycolide were mixed to prepare a support for tissue regeneration, and tensile strength, pH change, inflammatory response, and cytotoxicity were measured. . The results were similar to Example 1 as shown in Table 1.

Example 4:

Ring-opening polymerization was carried out in the same manner as in Example 1 using 10 parts by weight of barium hydroxide and 90 parts by weight of glycolide to prepare barium hydroxide particles whose surface was modified with polyglycolide.

30 parts by weight of the surface-modified barium hydroxide particles prepared by the above method and 70 parts by weight of polydioxanone were mixed to prepare nanofibers, and then tensile strength, pH change, inflammatory response, and cytotoxicity were measured. The results were similar to Example 1 as shown in Table 1.

Example 5:

20 parts by weight of potassium oxide and 80 parts by weight of caprolactone were subjected to ring-opening polymerization in the same manner as in Example 1 to prepare potassium oxide particles surface-modified with polycaprolactone.

Surface modified potassium oxide prepared by the above method Biosponge was prepared by mixing 95 parts by weight of particles with 5 parts by weight of polyglycolide, and then measured tensile strength, pH change, inflammatory response, and cytotoxicity. The results were similar to Example 1 as shown in Table 1.

Example 6:

Magnesium oxide particles having the surface modified with polylactide-co-caprolactone were prepared by ring-opening polymerization in the same manner as in Example 1 using 40 parts by weight of magnesium oxide and 42 parts by weight of lactide / 18 parts by weight of caprolactone.

Surface modified magnesium oxide prepared by the above method Hydrogel was prepared by mixing 35 parts by weight of particles with 65 parts by weight of polylactide-co-caprolactone, and then measured tensile strength, pH change, inflammatory response and cytotoxicity. The results were similar to Example 1 as shown in Table 1.

Example 7:

Condensation polymerization was carried out in the same manner as in Example 2 using 10 parts by weight of sodium oxide and 90 parts by weight of caproic acid hydroxide to prepare sodium oxide particles whose surface was modified with polycaprolactone.

10 parts by weight of the surface-modified sodium oxide particles prepared by the above method and 90 parts by weight of the polypeptide were mixed to prepare a neurosurgical material, and then tensile strength, pH change, inflammatory response and cytotoxicity were measured. The results were similar to Example 1 as shown in Table 1.

Example 8:

Magnesium hydroxide particles surface-modified with polyglycolide-co-caprolactone were subjected to condensation polymerization in the same manner as in Example 2 using 50 parts by weight of magnesium hydroxide and 25 parts by weight of glycolic acid / 25 parts by weight of caprohydric acid. Prepared.

Orthopedic materials were prepared by mixing 5 parts by weight of surface modified magnesium hydroxide particles prepared by the above method and 95 parts by weight of polydioxanone, and then measured tensile strength, pH change, inflammatory response and cytotoxicity. The results were similar to Example 1 as shown in Table 1.

Example 9:

Using 70 parts by weight of magnesium oxide and 30 parts by weight of polylactide, magnesium oxide particles whose surface was modified with polylactide were prepared by the core-shell method described in Example 3.

Surface modified magnesium oxide particles prepared by the above method A plastic surgery material was prepared by mixing 70 parts by weight and 30 parts by weight of polyhydroxyalkanoate, and then measured tensile strength, pH change, inflammatory response and cytotoxicity. The results were similar to Example 1 as shown in Table 1.

Example 10:

Using 20 parts by weight of cesium oxide and 80 parts by weight of polymaleic acid, the cesium oxide particles surface-modified with polymaleic acid were prepared by the core-shell method described in Example 3.

10 parts by weight of the surface-modified cesium oxide particles prepared by the above method and 90 parts by weight of polymaleic acid were mixed and coated on a cobalt-chromium stent to measure tensile strength, pH change, inflammatory response, and cytotoxicity. The results were similar to Example 1 as shown in Table 1.

Example 11:

The ring-opening polymerization was carried out in the same manner as in Example 1 using 70 parts by weight of calcium oxide and 30 parts by weight of lactide to prepare calcium oxide particles whose surface was modified with polylactide.

40 parts by weight of the surface-modified calcium oxide particles prepared by the above method was mixed with 60 parts by weight of polylactide and coated on a dental titanium-based implant. Tensile strength, pH change, inflammatory response and cytotoxicity were measured. The results were similar to Example 1 as shown in Table 1.

Example 12:

40 parts by weight of potassium hydroxide and 60 parts by weight of trimethylene carbonate were subjected to ring-opening polymerization in the same manner as in Example 1 to prepare potassium hydroxide particles whose surface was modified with polytrimethylene carbonate.

20 parts by weight of the surface-modified potassium hydroxide particles prepared by the above method was mixed with 80 parts by weight of polyglycolide to coat the apatite hydroxide orthopedic material. Tensile strength, pH change, inflammatory response and cytotoxicity were measured. The results were similar to Example 1 as shown in Table 1.

Example 13:

Condensation polymerization was carried out in the same manner as in Example 2 using 80 parts by weight of magnesium oxide and 20 parts by weight of caproic acid hydroxide to prepare magnesium oxide particles whose surface was modified with polycaprolactone.

50 parts by weight of the surface-modified magnesium oxide particles prepared by the above method was mixed with 50 parts by weight of polycaprolactone and coated on the surface of the non-degradable polyurethane stent. Tensile strength, pH change, inflammatory response and cytotoxicity were measured. The results were similar to Example 1 as shown in Table 1.

Comparative Example 1:

Samples were prepared using polylactide biodegradable polymers containing no metal particles. Tensile strength, pH change, inflammatory response and cytotoxicity were measured. As shown in Table 1, the tensile strength was relatively low, the pH remained acidic, the inflammatory response was very severe, and the cytotoxicity was remarkable.

Comparative Example 2:

Samples were prepared by mixing 5 parts by weight of magnesium hydroxide metal particles with no surface modification and 95 parts by weight of polylactide biodegradable polymer to measure tensile strength, pH change, inflammatory response and cytotoxicity. As shown in Table 1, the tensile strength was very low, the pH was slightly acidic, and the inflammatory response and cytotoxicity were somewhat suppressed.

Comparison of Properties of Matrix Containing Metal Particles division Neutralizing metal particles Tensile strength (MPa) pH (8 weeks) Inflammatory response Cytotoxicity Example 1 Surface modification 56 7.2 Full suppression X Example 2 Surface modification 57 6.8 Full suppression X Example 3 Surface modification 55 7.1 Full suppression X Example 4 Surface modification 57 6.9 Full suppression X Example 5 Surface modification 55 7.4 Full suppression X Example 6 Surface modification 54 7.1 Full suppression X Example 7 Surface modification 59 6.4 control △ Example 8 Surface modification 61 6.1 control △ Example 9 Surface modification 57 7.3 Full suppression X Example 10 Surface modification 53 6.3 control △ Example 11 Surface modification 57 6.4 control △ Example 12 Surface modification 55 6.9 Full suppression X Example 13 Surface modification 53 6.7 Full suppression X Comparative Example 1 Free 35 4.0 Very severe O Comparative Example 2 Unmodified surface 26 5.8 control △

(X: less than 10% cell death, △: cell death 10% ~ 30%, O: cell death 30% or more)

Claims (23)

A living implant comprising a basic metal particle surface modified with a polymer and a biodegradable polymer. The living body implant of claim 1, wherein the basic metal particles neutralize the acidic substance produced by the degradation of the biodegradable polymer, thereby inhibiting the inflammatory response. The method of claim 1, wherein the basic metal particles are selected from the group consisting of particles of metals selected from the group consisting of alkali metals and alkaline earth metals, hydroxides of alkali metals, oxides of alkali metals, hydroxides of alkaline earth metals and oxides of alkaline earth metals. The living implant is selected from the group consisting of particles of metal compounds. The living body implant of claim 3, wherein the alkali or alkaline earth metal is lithium, beryllium, sodium, magnesium, potassium, calcium, rubidium, strontium, barium, cesium, francium, or radium. The living implant of claim 1, wherein the metal particles have a diameter of 1 nm to 1 mm. The method of claim 1, wherein the surface-modified basic metal particles are lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate, alkanohydrate hydroxide, peptide, cyanoacrylate, lactic acid, glycolic acid, hydroxide Polymers or polylactides produced by the polymerization of one or more monomers selected from the group consisting of caproic acid, maleic acid, phosphazene, amino acids, butyric acid hydroxide, sebacic acid, ethoxyacetic acid hydroxide and trimethylene glycol, Polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone, polydioxanone, polytrimethylenecarbonate, polyglycola Id-co-dioxone, polyamide ester, polypeptide, polyorthoester type, polymaleic acid, polyphosphazene, polyanhydride, A living body implant, wherein the surface is modified with at least one polymer selected from the group consisting of polycebaanhydride, polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate. The method of claim 1, wherein the biodegradable polymer is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co- Caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxone, polyamide ester, polypeptide, polyol isoester type, polymaleic acid, polyphosphazene, polyanhydride, polyceva anhydride And at least one member selected from the group consisting of a lide, a polyhydroxyalkanoate, a polyhydroxybutyrate and a polycyanoacrylate. The living body implant of claim 1, wherein the basic metal particles surface-modified with the polymer contain 1 to 99 wt% of the polymer and 1 to 99 wt% of the basic metal particles. The living body implant of claim 1, wherein the living implant consists of a basic metal particle surface modified with a polymer and a biodegradable polymer. The bio-implant of claim 9 which contains 1 to 99% by weight of the basic metal particles surface-modified with a polymer and 1 to 99% by weight of the biodegradable polymer. 10. The dental or neuro / orthopedics / plastic surgeon of claim 9, wherein the cardiovascular material selected from stents, surgical sutures, tissue regeneration supports, bio nanofibers, hydrogels and bio sponges, pins, screws and rods The living implant is selected from the group consisting of biomaterials for use. The living body implant of claim 1, wherein the living body implant is coated with a basic metal particle that is surface modified with a polymer and a biodegradable polymer. The bio-implant of claim 12 wherein the coating contains from 1 to 99% by weight of basic metal particles surface-modified with a polymer and from 1 to 99% by weight of a biodegradable polymer, based on the total weight of the coating layer. The method of claim 12, wherein iron, copper, gold, silver, platinum, stainless steel, cobalt-chromium, platinum-chromium, cobalt, titanium, tantalum, nickel-titanium, nickel, magnesium, and alloys thereof, apatite hydroxide , TeCP, DCP, NaH ₂ PO ₄ , α-TCP, Glycerophosphate, PHA, Brushite, β-TCP, MCPM, MgHPO ₄ , Na ₄ P ₂ O ₇ and CaSO ₄ , Polyvinyl alcohol, polyvinyl chloride, polystyrene, polycarbonate, polyether ether ketone, polyamide, polyacetal, polythiophene, polyethylene oxide, polytetrafluoroethylene, acrylic resin, polyurethane, epoxy resin and polysiloxane Non-degradable polymers selected from, polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolye -co-caprolactone, polydioxanone, polytrimethylene carbonate, polyglycolide -co-dioxoneone, polyamide ester, polypeptide, polyol isoester type, polymaleic acid, polyphosphazene, polyanhydride, poly A bio-implant comprising a biodegradable polymeric material selected from the group consisting of sebacic anhydride, polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate. (a) modifying the surface of the basic metal particles with a polymer to obtain surface modified metal particles; and (b) mixing the surface modified metal particles with a biodegradable polymer to produce a biodegradable biograft. A method of making a living implant comprising a basic metal particle and a biodegradable polymer, surface modified with a furnace. The method of claim 15, wherein in step (a), monomers are ring-opened or condensation-polymerized at the surface of the basic metal particles, or the basic metal particle core is encapsulated in a core-shell form in the polymer shell to obtain surface modified metal particles. How. The method of claim 16, wherein the monomer is lactide, glycolide, caprolactone, dioxanone, trimethylene carbonate, alkanoate hydroxide, peptide, cyanoacrylate, lactic acid, glycolic acid, caprohydric acid, maleic acid , Phosphazene, amino acid, butyric acid hydroxide, sebacic acid, ethoxyacetic acid hydroxide and trimethylene glycol. The method of claim 16, wherein the polymer is polylactide, polyglycolide, polycaprolactone, polylactide-co-glycolide, polylactide-co-caprolactone, polyglycolide-co-caprolactone , Polydioxanone, polytrimethylene carbonate, polyglycolide-co-dioxone, polyamide ester, polypeptide, polyorthoester-based, polymaleic acid, polyphosphazene, polyanhydride, polycepha anhydride , At least one selected from the group consisting of polyhydroxyalkanoate, polyhydroxybutyrate and polycyanoacrylate. The method of claim 15, wherein in step (b), 5 to 95 parts by weight of the surface modified metal particles obtained in step (a) are mixed with 5 to 95 parts by weight of the biodegradable polymer. The method of claim 15, wherein instead of step (b), the method comprises mixing the surface modified metal particles obtained in step (a) with a biodegradable polymer and coating the surface of the living implant. Method of Making an Implant. The method of claim 20, wherein in step (b '), 5 to 95 parts by weight of the surface modified metal particles obtained in step (a) are mixed with 5 to 95 parts by weight of the biodegradable polymer. In a living implant, the surface-modified basic metal particles are contained in an amount of 1 to 99% by weight based on the total weight of the living implant to remove acidic substances generated upon decomposition of the living implant using an acid-base neutralization reaction. . The bio-implant contains the surface-modified basic metal particles in an amount of 1 to 99% by weight based on the total weight of the bio-implant, thereby suppressing the interfacial separation between the metal and the biodegradable polymer, thereby making the bio-degradable bio-implant implant Or improving the mechanical properties of a biodegradable polymer coating layer coated on a living implant.